Pilot Project Abstract - Vu, Tania, PhD

The Center for Disease Control (CDC) ranks lung cancer among the three leading causes of cancer mortality in the United States alone. Imaging technologies such as CT, MRI, and PET provide the cornerstone for diagnosis and therapeutic treatment and hold great promise. However, these advanced imaging approaches rely on anatomic rather than quantitative, functional-based agents to image tissue. Currently, it is not possible to accurately stage disease (e.g. when metastases progress without anatomic change) and to clearly differentiate between tumor or non tumor tissues. As a result, the prognosis for those with lung cancer remains poor (15% survival at 5 years, 45-70% recurrence rates in stage I and II). The long-term goal of this project is to develop a functional, high-contrast magnetic resonance imaging (MRI) probe for cell-specific imaging and targeting of lung tumors. We propose to synthesize and test a multi-functional nanoparticle probe consisting of a quantum dot (QD) carrier platform to which anti-epidermal growth factor receptor (anti-EGFR) antibody (Ab) and gadolinium (Gd) chelates are bound (QD- anti-EGFR Ab-Gd). The QD is nanoparticle with small size (~15 nm) that will allow its facile entry to tissue targets. Moreover, the QD nanoparticle has intrinsic fluorescence that will allow quantitative, post-histological evaluation of QD probe-EGF receptor (EGFR) targeting and correlation to MRI signal in the same cell samples. Finally, conjugation of multiple Gd chelates to each QD will provide a high positive contrast signal - as opposed to iron oxide-based nanoparticles which are problematic in lung tumor imaging since they cannot be differentiated from normal lung tissue due to the appearance of a dark signal on MRI images.